Design, synthesis, crystal structure, and herbicidal activity of novel pyrrolidine-2,4-dione derivatives incorporating an alkyl ether pharmacophore with natural tetramic acids as lead compounds

Abstract

In order to discover green herbicides with novel molecular scaffolds, natural tetramic acids were used as lead compounds to design and synthesize four pyrrolidine-2,4-dione derivatives incorporating a chainlike alkoxyalkyl moiety (4a–4d) and nineteen pyrrolidine-2,4-dione derivatives incorporating a substituted phenoxyethyl moiety (10a–10s) via substitution, acylation, cyclization, and acidification reactions. The synthesized target compounds were confirmed by FT-IR, ¹H NMR, ¹³C NMR and HRMS spectral analyses. The single-crystal structure of compound 10a was analyzed by X-ray diffraction, which revealed that the 1-hydroxyethylidene group links the third position of the pyrrolidine heterocycle through a double bond with the Z-configuration. The herbicidal activity was evaluated using barnyard grass (Echinochloa crus-galli) and rape (Brassica campestris) as model plants by a Petri dish culture method. Most target compounds were found to possess moderate to good inhibitory activities against the plant growth at 100 μg mL⁻¹. Among them, the compounds 10q and 10n showed the highest herbicidal activities against the roots of barnyard grass and rape seedlings with the corresponding inhibition rates of 65.6% and 84.0%, respectively. This result indicated that pyrrolidine-2,4-dione derivatives incorporating a substituted phenoxyethyl moiety are worthy of further structural optimization.